Project Summary The objective of this application is to obtain funds to purchase a stimulated emission depletion (STED) super- resolution microscope, the Leica TCS SP8 STED 3X, for the Confocal Imaging Facility at the University of Kansas Medical Center's Lied Building. This Confocal Imaging Facility is part of the imaging core facility, which has been in operation since 1972 with light and electron microscopes, receives annual financial support from the University of Kansas Medical Center and is staffed by personnel with excellent technical expertise. This facility has confocal (Leica SPE and Zeiss LSM 510) and electron (JOEL JEM-1400 TEM, Hitachi S-2700 SEM) microscopes, along with the necessary equipment to carry out a wide range of light and electron microscopy experiments. However, neither this facility nor any lab on the University of Kansas Medical Center campus possesses any type of super-resolution microscope (STED, STORM/PALM, SIM). Multiple NIH-funded investigators studying the mechanisms underlying diverse health-related topics at the University of Kansas Medical Center are in great need of a super-resolution microscope with subdiffraction-limited resolution. These include projects that examine (1) synaptic proteins in aging and amyotrophic lateral sclerosis (ALS), (2) the mechanism of parvovirus gene expression and replication, (3) the ciliary localization of proteins in cystic kidney disease, (4) adherens junction and cell adhesion molecules in craniofacial defects, (5) cellular-trafficking- receptor localization in diabetic dyslipidemia, (6) ciliary protein localization analysis, (7) autophagosomes and mitophagy in liver injury, (8) tyrosine kinases and signaling proteins in fertilization and (9) mitochondrial RNA defense pathways in the oocytes. Two of these projects have published with STED microscopy data, and six projects are currently using the Leica TCS SP8 STED 3X microscope at the Univ. Missouri-Columbia, Molecular Cytology Core (about 5-hour round trip drive from Univ. Kansas Sch. Medicine). Progress on all these projects will be significantly enhanced by the availability of the Leica TCS SP8 STED 3X super-resolution microscope at our imaging core facility. In addition, the confocal microscope capability of the requested equipment will replace the retiring confocal microscope Zeiss LSM 510 (purchased in 1999), which is no longer supported by the manufacturer.